A Cross-Sectional Study Examining the Parametric Thyroid Feedback Quantile Index and Its Relationship with Metabolic and Cardiovascular Diseases

Abstract

Background: The usual inverse correlation between thyrotropin (TSH) and thyroid hormone disappears in syndromes of central resistance to thyroid hormone, where both are high. TSH and thyroid hormone are also simultaneously high when there is an elevation of the set point of the thyroid regulation axis. This can be estimated with indices, such as the Parametric Thyroid Feedback Quantile-based Index (PTFQI), which was designed for the general population. The PTFQI is positively associated with diabetes prevalence, but association with other pathologies has not been yet explored. The aim of this project was to explore the potential relationship of the PTFQI with metabolic and cardiovascular disease in a sample of ambulatory adult patients from Spain. Methods: A cross-sectional study was carried out among the patients who underwent thyroid hormones measurement (6434 measurements from September to November 2018 in a central laboratory in Spain). We retrospectively reviewed clinical records of a subgroup of adults aged >18 years with normal TSH and free thyroxine (fT4) belonging to groups that represent extreme PTFQI ( n = 661). Individuals with known conditions interfering the thyroid axis were excluded (remaining n = 296). Logistic and linear regression models adjusted for age and sex were used to calculate odds ratio (OR) of diseases and differences of clinical parameters, and 95% confidence intervals [CI]. Results: Across levels with higher PTFQI, there was an increase in the prevalence of type 2 diabetes (High vs. Low PTFQI OR: 2.88 [CI: 1.14–7.86], p -Trend = 0.02), ischemic heart disease (16.4% vs. 0%, unadjusted Haldane–Anscombe corrected OR: 23.90 [CI: 1.36–21.48], adjusted p -Trend = 0.04), atrial fibrillation (OR: 8.13 [CI: 1.33–158.20], p -Trend = 0.05), and hypertension (OR: 3.19 [CI: 1.14–9.94], p -Trend = 0.05). While the prevalence of type 2 diabetes was similarly associated with TSH and fT4, ischemic heart disease, atrial fibrillation, and hypertension were more strongly associated with the differences in fT4 values. Conclusions: Type 2 diabetes, ischemic heart disease, atrial fibrillation, and hypertension may be associated with a higher central regulation set point for thyroid hormone. These findings should be confirmed in other populations.

An elevated parametric thyroid feedback quantile-based index is associated with atrial fibrillation

“…Thus, investigating whether altered thyroid regulation is related to atrial fibrillation, beyond the already known effects of primary hyperthyroidism, becomes relevant. Indeed, our previous results (14) encourage researching this association. Thyroid regulation can be studied with biochemical indexes.…”

“…Thyroid parameters of healthcare patients older than 18 years who underwent a thyroid hormone measurement across three months of 2018, in the central laboratory of the Miguel Servet University Hospital (6051 patients) were used to calculate the reference parameters for the PTFQI formula (14). Euthyroid participants of this sample constituted the control group (n=5256).…”

“…The PTFQI (14,15) is calculated with a formula: f ((fT4 -µ fT4 )/ s fT4 ) -(1-f ((ln TSH -µ ln TSH )/s ln TSH ))), where µ fT4 = 11.49 pmol/L, s fT4 = 2.46 pmol/L, µ ln TSH = 0.55, and s ln TSH = 1.00 in our reference sample (see above).…”

“…Thyroid regulation can be studied with biochemical indexes. In particular, the Parametric Thyroid Feedback Quantile-Based Index (PTFQI) (14,15) quantifies the deviations from the physiological population-average pituitary response to thyroid hormone and ranges from -1 to 1: negative values indicate an abnormally low TSH for fT4 values (a down-regulated TSH-inhibition threshold) and positive values indicate an abnormally high TSH given fT4 levels (an upregulated TSH-inhibition threshold).…”

Editorial: Thyroid hormones and cardiac arrhythmia

“…According to the available evidence, even slight deviations of thyroid hormones confer significant risks for MACE, including malignant arrhythmia. Advanced diagnostical strategies should address the whole feedback loop to avoid misinterpretation by allostatic load, hysteresis and other effects, and modern therapeutic measures should involve multimodal approaches ( 21 – 23 , 33 – 37 ). This is of particular importance due to the biological potency and relatively long plasma half-life of thyroid hormones.…”